一种喹唑啉酮(苯并咪唑及苯并噻唑)类化合物的通用合成方法

今天分享的内容是一种喹唑啉酮,苯并咪唑及苯并噻唑类结构的构建方法，作者以亚磷酸为催化剂，β-酮酯类化合物与邻氨基苯甲酰胺(邻氨基苯胺及邻氨基苯硫酚)发生环合反应生成相应的产物。该方法的反应条件温和，底物普适性较广，可达到中等及以上收率，对以上三类结构的构建具有十分重要的意义。

该文献报道的方法及操作

操作:A 5 mL Schlenk tube equipped with a magnetic stir bar was charged with o-aminophenyl derivative (1, 5, or 6 0.2 mmol), β-diketone/ketoester (2 or 4 0.26 mmol), H3PO3(0.02 mmol, 10 mol %), and ethanol (0.5 mL).The reaction mixture was stirred at 50 °C for 15 h. The reaction was monitored by GC or GC-MS. After completion of the reaction, the resulting solution was cooled to room temperature, and neutralized with saturated solution of NaHCO3.The product was extracted with EtOAc, dried over anhydrous Na2SO4,and concentrated in vacuo. The crude product was purified by flash column chromatography(eluent:ethyl acetate/petroleum ether = 1/2-1/5) on silica gel to afford the desired product.

底物普适性考察

aReaction conditions: 2-aminobenzamide 1 (0.2 mmol), β-ketoester2 (0.26 mmol), 50% H3PO3 (10 mol %, 0.02 mmol), EtOH (0.5mL) in 5 mL Schlenk tube, 50 °C, 15 h. bIsolated yield. c80°C, 24 h. d100 °C, 24 h.

aReaction conditions: 2-aminobenzamide 1 (0.2 mmol), β-diketone4 (0.26 mmol), 50% H3PO3 (10 mol %, 0.02 mmol), EtOH (0.5mL) in 5 mL Schlenk tube, 50 °C, 15 h. bIsolated yield. c80°C, 24h. d100 °C, 24 h. e130 °C, 24 h.

aReaction conditions: o-substituted aniline 5 or 6 (0.2 mmol), β-ketoester 2 (0.26 mmol), 50% H3PO3 (10 mol %, 0.02 mmol),EtOH (0.5 mL) in 5 mL Schlenk tube, 50 °C, 15 h. bIsolated yield.c80 °C, 24 h.

反应机理的探究及推测

作者通过采用捕捉反应中间态的方法，对反应的机理进行研究。如下图:

反应6h，底物1a几乎消耗完全，GC产率产物3a占比36%，中间态la占比57%；反应15h，底物1a和中间态la几乎都完全转化为了产物3a，GC产率大于99%。

可能存在的机理

以上图片及表格均来自于参考文献

参考文献:DOI: 10.1021/acs.joc.5b00937